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H pylori infection

Protein could play a key role in response to H pylori infection

Helicobacter pylori is the dominant member of the gastric microbiota in more than 50% of the world’s population
Using a combined computational and experimental approach the researchers demonstrated how IL-21 may play a key role in immune responses to H pylori infection

Scientists from the Virginia Bioinformatics Institute at Virginia Tech and Vanderbilt University have made steps toward understanding the immune response involved in Helicobacter pylori infection, according to a study ‘Systems Modeling of the Role of Interleukin-21 in the Maintenance of Effector CD4+ T Cell Responses during Chronic Helicobacter pylori Infection’, published in mBio.

Helicobacter pylori is the dominant member of the gastric microbiota in more than 50% of the world’s population, and its colonisation has been implicated in gastritis and gastric cancer, as infection with H. pylori is the single most common risk factor for gastric cancer. Current data suggest that, in addition to bacterial virulence factors, the magnitude and types of immune responses influence the outcome of colonisation and chronic infection.

Using a combined computational and experimental approach, the researchers demonstrated how a protein known as IL-21 may play a key role in immune responses to H pylori infection.

"Applying systems computer modelling allows us to predict which signalling pathways and T cell responses are impacted by IL-21," said Holly Algood, an assistant professor at Vanderbilt University and a senior and corresponding author of the study. "With this greater understanding, we can refine and better focus our experimental efforts."

IL-21 plays a critical role in immune response to infection. It is produced by a variety of immune cells and has anti-tumor and anti-viral properties. However, it also leads to excessive inflammation and the immune and inflammatory responses triggered by the bacteria are far worse than the infection itself, and it is these responses that lead to pathology and disease.

"Although IL-21 is helpful in many ways, in the case of H pylori infections, it can exacerbate damage to the stomach. Computational modelling has helped us determine how the IL-21 pathway affects inflammation, and this will lead to the development of better therapies," said Adria Carbo, first author of the study and a researcher with the Center for Modeling Immunity to Enteric Pathogens at the Virginia Bioinformatics Institute.

"The computational models we've developed have greatly increased understanding of the role of IL-21 in modulating immune responses to pathogens," said Raquel Hontecillas, co-director and immunology leader of the centre. "We can now move toward development of IL-21-based host-targeted therapeutics against infectious and immune-mediated diseases."

Previous work from the center has focused on creating computational models that have helped researchers better understand the dual role of H pylori as a pathogen and a beneficial member of the gastric microbiota.

However, many studies have suggested that H pylori plays a beneficial role, protecting against childhood allergies, childhood asthma, obesity, and diabetes. Although doctors currently use antibiotics to treat H pylori-caused disease, some scientists argue that overuse of antibiotics may result in development of antibiotic resistance, making the infection more difficult to treat.

"The collaboration between Vanderbilt and Virginia Tech opens new possibilities for understanding the pathology of H pylori infection," said Josep Bassganya-Riera, director of the centre and also a corresponding author of the study. "Building on the foundation of computational models developed by the Center for Modeling Immunity to Enteric Pathogens, our team effort allows us to gain vital new knowledge about mechanisms of action as well as translation of our computational modeling and bioinformatics innovations to the clinic."

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